The fundamental goal of this proposal is to investigate how human B cell activation and growth are regulated through cell surface molecules. We will focus on characterizing the ligands and signal transduction pathways induced via three major B cell-associated surface molecules, namely CD20, CD40 and Bgp95. We will make use of a set of agonistic monoclonal antibodies (mAb) to these markers and full length cDNAs in expression vectors encoding CD20 and CD40. Our specific aims are: Aim 1) to define the ligands for CD20 and CD40, making use of cell lines transformed with either CD20 or CD40; Aim 2) to characterize the signal transduction pathways for CD20 and CD40 by measuring inositol phospholipid metabolism, protein kinases and/or anti-CD40; Aim 3) to isolate cDNAs encoding Bgp95 for use in characterizing the structure and function of this surface molecule involved in the regulation of B cell activation; and Aim 4) to assess the role that the membrane protein tyrosine phosphatase (PTPase) CD45 plays in regulating competence (CD20, Bgp95) and progression (CD40) signals in human B cells. These studies will help to elucidate not only the basic mechanisms regulating small resting B cells, but will also provide new information on how the transition of G0 to the Gl phase of the cell cycle is controlled.